This invention relates to the detection of biological particles by the utilization of the phenomenon by which such biological particles interact specifically either immunologically or non-immunologically.
Constructions of diagnostic devices for use in the immunological detection of proteins are disclosed in the related copending U.S. Applications of Giaever, Ser. No. 384,113, filed July 30, 1973 (now abandoned) and Ser. No. 445,204, (now U.S. Pat. No. 3,926,564) filed Feb. 25, 1974. In both of these constructions the outer surface consists of a layer of preselected proteins specifically interactive with the protein of interest. In Ser. No. 384,113, the substrate surface to which the preselected protein layer is applied is preferably metallic. In Ser. No. 445,204 the substrate surface to which the preselected protein layer is applied is made up predominately of metallic oxide, which metallic oxide may contain minute matallic particles. The aforementioned copending applications are assigned to the assignee of this invention and are incorporated herein by reference.
The preselected protein layer absorbs on to the surface of the substrate in a monomolecular layer. When a suspected solution is to be tested for the presence or absence of the protein of interest, the monomolecular protein layer is placed in contact with the solution for a sufficiently long period of time to permit the specific reaction to occur if the protein of interest is present. Wherever the specific reaction occurs, the resulting complex between the initial protein layer and the protein of interest results in a bimolecular protein layer. No protein other than the protein of interest will adhere to the initial protein layer. Detection of the presence of a bimolecular layer as contrasted to a monomolecular layer follows.
Those publications related to the present invention primarily as background are "Optical Measurement of the Thickness of a Film Adsorbed from a Solution" by Irving Langmuir et al. [Journal of the American Chemical Society, Vol. 59 (July-Dec. 1937) page 1406]; "Immunological Reactions Carried Out At a Liquid-Solid Interface" by A. Rothen et al. [Helvetica Chimica Acta - Vol. 54, Fasc 4 (1971)-Nr. 123, pages 1208-1217]; "Blood Coagulation Studies With the Recording Ellipsometer" by L. Vroman [National Bureau of Standards Miscellaneous Publication 256, September 1964]; "Immunological Reactions Between Films of Antigen and Antibody Molecules" by A. Rothen [Journal of Biological Chemistry, Vol. 168, pages 75-97 (April, May 1947)]; "Findings With the Recording Ellipsometer Suggesting Rapid Exchange of Specific Plasma Proteins at Liquid/Solid Interfaces" by L. Vroman et al. [Surface Science 16 (1969), pages 438-446]; "Immunologic and Enzymatic Reactions Carried Out at a Solid-Liquid Interface" by Alexandre Rothen [Physiological Chemistry and Physics, 5, (1973) pages 243-258]; "Interactions Among Human Blood Proteins at Interfaces" by Leo Vroman et al. [Federation Proceedings, Vol. 30, No. 5 (Sept.-Oct. 1971) pages 1494-1502]; "The Antibody-Antigen Reaction: A Visual Observation" by Ivar Giaever [The Journal of Immunology, Vol. 110, No. 4 (May 1973) pages 1424-1426]; "Effects of Hydrophobic Surfaces Upon Blood Coagulation" by L. Vroman [Thromb. Diath, Haemorrhag., Vol. 10, pages 455-493 (1964)] and "Three Simple Ways to Detect Antibody-Antigen Complex on Flat Surfaces" by A. L. Adams et al. [Journal of Immunological Methods 3 (1973) pages 227-232].
The term "biological particle" is intended to encompass smaller proteins (e.g. plasma proteins, antigens, antibodies, lactins) and bodies of proteinaceous material (e.g. viruses, bacteria, cells) capable of stimulating antibody production, when injected into an animal, and/or having the property of interacting specifically either immunologically or non-immunologically.